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Toxicological information

Carcinogenicity

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Description of key information

No relevance of carcinogenic effect/potential

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Remarks:
read across on structural analogue
Adequacy of study:
weight of evidence
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study is old, not GLP, but well described and scientifically valid
Qualifier:
according to
Guideline:
EU Method B.32 (Carcinogenicity Test)
Deviations:
not specified
GLP compliance:
no
Species:
mouse
Strain:
Strain A
Sex:
male/female
Details on test animals and environmental conditions:
Male and female inbred ST/a mice, originating from the Fibiger Laboratory and bred in our laboratory, were housed in macrolone cages and fed a pellet stok diet (Rostock mixture, Copenhagen) with water ad libitum. Preliminary experiments using hair colouring and skin biopsies showed that the second resting phase of the hair cycle started at about 45 days of age. Consequently the application of test substances was started when animals were 6.5 to 8 weeks old. Males then weighed about 20 g, females about 15 g
Route of administration:
oral: feed
Vehicle:
other: incorporated in food
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
300 days
Frequency of treatment:
1/2 a day
Post exposure period:
28 weeks
Remarks:
Doses / Concentrations:
15 mg/day
Basis:
nominal in diet
No. of animals per sex per dose:
30 in total
Control animals:
yes, concurrent no treatment
other: same induction, no treatment
Details on study design:
Initiating was performed giving a solution of 4-nitroquinoline 1- oxide (NQO) trough stomach tube three times a week for two weeks. Each intubation was done in the morning and had been preceded by 17 hors of fasting. The initial dose was 0.1 mg, the following doses were 0.2 mg each.
Observations and examinations performed and frequency:
The animals were inspected and weighted once every two weeks
Sacrifice and pathology:
Surviving animals after 300 days were killed at 84 weeks. Authopsy was performed on all mice. The stomach, spleen, left kidney, liver, lungs and hearth were routinely examined histologically
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
8 death on 30 after 54 weeks
Mortality:
mortality observed, treatment-related
Description (incidence):
8 death on 30 after 54 weeks
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
See table below
Relevance of carcinogenic effects / potential:
No relevance of carcinogenic effect/potential

Initiator Promoter N° of mice Survivors at 57 weeks Survivors at 84 weeks N° mice with lymphoma N° mice with papilloma N° of papillomas
None None 30 20 9 2 0 0
NQO None 30 19 5 2 4 4
NQO Methyl oleate 30 22 15 2 5 8
Conclusions:
No relevance of carcinogenic effect/potential
Executive summary:

Two fatty acid methyl esters, methyl oleate and methyl 12-oxo-trans-10-octadecenoate, have been tested for carcinogenicty by oral and subcutaneous administration in ST/a mice of both sexes. A positive effect of methyl oleate could not be assessed, while the results pointed to a promoter effect of methyl oxo-octadecenoate. Given in the diet, this compound increased the incidence and number of forestomach papillomas within 83 weeks after initiation by 4-nitroguinoline 1-oxide.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Carcinogenicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
carcinogenicity: dermal
Type of information:
experimental study
Remarks:
read across on structural analogue
Adequacy of study:
weight of evidence
Study period:
1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is old and with some details missing.
Qualifier:
no guideline followed
Qualifier:
equivalent or similar to
Guideline:
EU Method B.32 (Carcinogenicity Test)
Deviations:
yes
Remarks:
Only one year dosing
GLP compliance:
no
Species:
mouse
Strain:
Strain A
Sex:
male/female
Details on test animals and environmental conditions:
The animal were fed a commercial pellet stock diet
The applications started when the animals were 6.5-8 weeks old within a resting phase of their hair cycle
Route of administration:
dermal
Vehicle:
acetone
Details on exposure:
3 times per week applied by means of a syringe to the interscapular region of each animal
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
1 year
Frequency of treatment:
3 times per week
Post exposure period:
no
Remarks:
Doses / Concentrations:
10 micrograms
Basis:
nominal conc.
No. of animals per sex per dose:
35 animals in total
Control animals:
yes, concurrent no treatment
Details on study design:
Initiation was accomplished by a single application of 50 micrograms dimethylbenzanthracene. A control group of animals was given the effectively dose of 250 micrograms.
Promotion was started 2 weeks after initiation. Croton oil was used as positive control promoter. Animals to which no promoter was applied served as negative control group. Further control groups were given the same tretments with respect to promoters but without previous initiation. The animals were inspected weekly.
Papillomas were counted when at least 1 mm in diameter and observed for 3 weeks in succession.
Dead mice were autopsied and tmors xamined histologically
Observations and examinations performed and frequency:
Animals were inspected once a week
Sacrifice and pathology:
Dead mice were autopsied and tmors xamined histologically
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
at 12 months survivors are 82% while the control are 64%
Mortality:
mortality observed, treatment-related
Description (incidence):
at 12 months survivors are 82% while the control are 64%
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
See table below
Relevance of carcinogenic effects / potential:
No relevance of carcinogenic effect/potential
Dose descriptor:
NOAEC
Remarks on result:
not determinable
Remarks:
no NOAEC identified. Effect type:carcinogenicity (migrated information)
Conclusions:
No relevance of carcinogenic effect/potential
Executive summary:

Methyl 12 -oxo-trans-10 -octadecenoate and methyl hydroxyoctadecadienoate were tested for carginogenic and tumor promoting activity on mouse skin. Methyl oleate, which was inactive in the preliminary screening was also tested. No safe evidence of any proper carcinogenic effect of the fatty acid esters was found; some degree of tumor promoting activity could be further investigated

Endpoint:
carcinogenicity: dermal
Type of information:
experimental study
Remarks:
read across on structural analogue
Adequacy of study:
weight of evidence
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study is old, not GLP, but well described and scientifically valid
Qualifier:
according to
Guideline:
EU Method B.32 (Carcinogenicity Test)
Deviations:
yes
GLP compliance:
no
Species:
mouse
Strain:
Strain A
Sex:
male/female
Details on test animals and environmental conditions:
Male and female inbred ST/a mice, originating from the Fibiger Laboratory and bred in our laboratory, were housed in macrolone cages and fed a pellet stok diet (Rostock mixture, Copenhagen) with water ad libitum. Preliminary experiments using hair colouring and skin biopsies showed that the second resting phase of the hair cycle started at about 45 days of age. Consequently the application of test substances was started when animals were 6.5 to 8 weeks old. Males then weighed about 20 g, females about 15 g
Route of administration:
dermal
Vehicle:
acetone
Details on exposure:
3 times per week applied by means of a syringe to the interscapular region of each animal
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
1 year
Frequency of treatment:
3 times a week
Post exposure period:
1 year
Remarks:
Doses / Concentrations:
0.01 mg
Basis:
nominal conc.
No. of animals per sex per dose:
35 in total
Control animals:
yes, concurrent no treatment
Details on study design:
Initiation was accomplished by a single application of 50 micrograms dimethylbenzanthracene.
Promotion was started 2 weeks after initiation. Croton oil was used as positive control promoter. Animals to which no promoter was applied served as negative control group. Further control groups were given the same tretments with respect to promoters but without previous initiation. The animals were inspected weekly.
Papillomas were counted when at least 1 mm in diameter and observed for 3 weeks in succession.
Dead mice were autopsied and tumors examined histologically
Positive control:
Croton oil was used as positive control promoter
Observations and examinations performed and frequency:
Papillomas were counted when at least 1 mm in diameter and observed for 3 weeks in succession.
Dead mice were autopsied and tumors examined histologically
Autopsy was performed on all mice, and the interscapular skin, left kidney, spleen, liver, heart and lungs were routinely processed for histological study. Papillomas were confirmed histologically if not regressed before the death of the animal.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
9 survivolrs females after 24 months
Mortality:
mortality observed, treatment-related
Description (incidence):
9 survivolrs females after 24 months
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
Twelve of 13 cases of amyloidosis were seen in male mice and thy shoed a high fighting activity. The amylosis was then correlated with wounding and stress in submissive male mice
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
See table below
Relevance of carcinogenic effects / potential:
No relevance of carcinogenic effect/potential
Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
no NOAEL identified. Effect type:carcinogenicity (migrated information)

Initiator Promoter N° of mice Survivolrs at 24 months N° mice with lymphoma Days to first skin tumor
None None 25 8 4 712
None Methyl oleate 35 9 9 406
DMBA None 20 4 2 667
DMBA Methyl oleate 30 0 2 239
Conclusions:
No relevance of carcinogenic effect/potential
Executive summary:

Methyl 12 -oxo-trans-10 -octadecenoate and methyl hydroxyoctadecadienoate were tested for carginogenic and tumor promoting activity on mouse skin. Methyl oleate, which was inactive in the preliminary screening was also tested. No safe evidence of any proper carcinogenic effect of the fatty acid esters was found; some degree of tumor promoting activity could be further investigated

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

No relevance of carcinogenic effect/potential

Justification for classification or non-classification

All studies are of poor quality and of questionable relevance.

1.1.1    Conclusion

No classification for carcinogenicity warranted under 67/548/EEC or Regulation 1272/2008.